The cationic PLL-Fe2o3/SiO2-siRNA nanoparticles with an average crystallite size of about 20 nm were prepared and delivered into primary rat neurons for knockdown of gene expression. Primary rat fetal neurons were scratched to simulate the injury of central nervous system and then were transfected with PLL-Fe2O3/SiO2-siRNA nanoparticles. Optical microscopy, fluorescence microscopy, Western blotting, immunofluorescence, and MTT assays were employed to test the cytotoxicity, the efficiency of encapsulation and targeted gene silencing. The results indicated that the PLL-Fe2O3/SiO2-siRNA nanoparticles have a remarkable efficiency of encapsulation and targeted gene silencing with negligible cytotoxicity. It could be concluded that the PLL-Fe2O3/SiO2 nanoparticles are a promising delivery carrier of siRNA.